Hipocalcemia, hipomagnesemia y uso crónico de inhibidores de la bomba de protones / Hypocalcemia, hypomagnesemia, and chronic use of proton pump inhibitors

Introducción: Los inhibidores de la bomba de protones son fármacos usados en múltiples gastropatías. El omeprazol pertenece a este grupo de medicamentos y es aprobado y catalogado como indispensable por la Organización Mundial de la Salud. Esto ha causado que su uso se vuelva constante y hasta cierto punto equívoco. Pese a ser medicamentos seguros muestran efectos secundarios, dentro de los cuales uno ocasional es el trastorno hidroelectrolítico. Objetivo: Presentar un caso clínico en el cual se constató la presencia de efectos secundarios tras el uso de un fármaco de uso constante por la comunidad médica: el omeprazol. Caso clínico: Se presenta a continuación el caso clínico de un paciente masculino con antecedente de hipertensión arterial y gastropatía crónica que muestra uso por 8 años consecutivos de inhibidores de la bomba de protones, al cual se le diagnostica hipomagnesemia e hipocalcemia. Se obtuvieron resultados de laboratorio normales tras administración de suplementos orales y uso de ranitidina con supresión de terapéutica con omeprazol. Conclusiones: Un control constante de los fármacos que usan los pacientes crónicos es fundamental en atención primaria de salud. El uso de inhibidores de la bomba de protones se ha convertido en rutinario y es necesario corroborar siempre la dosis y el tiempo de uso de los fármacos además de la relación con otros medicamentos que use el paciente(AU)

Introduction: Proton-pump inhibitors are drugs used in multiple gastropathies. Omeprazole belongs to this group of medicines; it is approved and classified as essential by the World Health Organization. This has permitted for its use to become constant and, to some extent, misleading. Despite being safe drugs, they show side effects, among which an occasional one is fluid and electrolyte disorders. Objective: To present a clinical case in which the occurrence of side effects was verified after the administration of a drug constantly used by the medical community. Clinical case: The following is a clinical case of a male patient with a history of arterial hypertension and chronic gastropathy, characterized by the usage of proton-pump inhibitors for eight consecutive years, diagnosed with hypomagnesemia and hypocalcemia. Normal laboratory results were obtained after oral supplementation and usage of ranitidine with suppression of omeprazole therapy. Conclusions: Constant control of the drugs used by chronic patients is essential in primary health care. The usage of proton-pump inhibitors has become a routine. It is always necessary to check the dose and time for using the drugs as well as the relationship with other drugs used by the patient(AU)

Incidence of postoperative dyspepsia is not associated with prophylactic use of drugs / Incidência de dispepsia pós-operatória não está associada com uso profilático de medicamentos

CONTEXT AND OBJECTIVE: Preoperative fasting guidelines do not recommend H2 receptor antagonists or proton pump inhibitors. This study investigated prophylactic use of gastric protection and the incidence of dyspeptic symptoms in the immediate postoperative period. DESIGN AND SETTING: Non-randomized observational investigation in a post-anesthesia care unit. METHODS: American Society of Anesthesiologists risk classification ASAP1 and ASAP2 patients over 18 years of age were evaluated to identify dyspeptic symptoms during post-anesthesia care for up to 48 hours, after receiving or not receiving prophylactic gastric protection during anesthesia. History of dyspeptic symptoms and previous use of such medications were exclusion criteria. The odds ratio for incidence of dyspeptic symptoms with use of these medications was obtained. RESULTS: This investigation studied 188 patients: 71% women; 50.5% ASAP1 patients. Most patients received general anesthesia (68%). Gastric protection was widely used (n = 164; 87.2%), comprising omeprazole (n = 126; 76.8%) or ranitidine (n = 38; 23.2%). Only a few patients did not receive any prophylaxis (n = 24; 12.8%). During the observation, 24 patients (12.8%) reported some dyspeptic symptoms but without any relationship with prophylaxis (relative risk, RR = 0.56; 95% confidence interval, CI: 0.23-1.35; P = 0.17; number needed to treat, NNT = 11). Omeprazole, compared with ranitidine, did not reduce the chance of having symptoms (RR = 0.65; 95% CI: 0.27-1.60; P = 0.26; NNT = 19). CONCLUSION: This study suggests that prophylactic use of proton pump inhibitors or H2 receptor antagonists was routine for asymptomatic patients and was not associated with postoperative protection against dyspeptic symptoms. .

CONTEXTO E OBJETIVO: Diretrizes para jejum pré-operatório não recomendam antagonistas dos receptores H2 ou inibidores da bomba de prótons. Este estudo investigou o uso profilático de proteção gástrica e a incidência de sintomas dispépticos no período pós-operatório imediato. TIPO DE ESTUDO E LOCAL: Estudo observacional não aleatorizado em unidade de recuperação pós-anestésica. MÉTODOS: Pacientes ASAP1 e ASAP2, classificação de risco da American Society of Anesthesiologists, com mais de 18 anos de idade, foram avaliados para identificar sintomas dispépticos durante a recuperação pós-anestésica em até 48 horas, tendo ou não recebido proteção gástrica profilática durante a anestesia. História de sintomas dispépticos e uso prévio de tais medicamentos foram critérios de exclusão. A razão de chances para incidência de sintomas dispépticos com uso desses medicamentos foi obtida. RESULTADOS: Foram estudados 188 pacientes, 71% mulheres, 50,5% dos pacientes ASAP1. A maioria dos pacientes recebeu anestesia geral (68%). Proteção gástrica foi amplamente usada (n = 164; 87,2%), consistindo de omeprazol (n = 126; 76,8%) ou ranitidina (n = 38; 23,2%). Poucos pacientes não receberam qualquer profilaxia (n = 24; 12,8%). Durante a observação, 24 pacientes (12,8%) relataram alguns sintomas dispépticos, porém sem relação com profilaxia (risco relativo, RR = 0,56; intervalo de confiança, IC 95% 0,23-1,35, P = 0,17; número necessário para tratar, NNT = 11). Omeprazol, comparado à ranitidina, não reduziu a chance de ter sintomas (RR = 0,65; IC 95% 0,27-1,60; P = 0,26; NNT = 19). CONCLUSÃO: Este estudo sugere que o uso profilático de inibidores da bomba de prótons ...

Pharmacological efficacy of argemone mexicana plant extract, against cysteamine-induced duodenal ulceration in rats.

Objective: The plant Argemone mexicana is traditionally used as diuretic, anti-inflammatory, antibacterial, antifungal agent, and has wound-healing property. This study was carried out to evaluate the effect of A. mexicana aerial part of the plant (methanolic and aqueous extract p.o.) on duodenal ulceration. Materials and Methods: The study was carried out on the duodenal ulceration model by using cysteamine hydrochloride. Ranitidine (20 mg/kg) was used as standard drug. Results: Both the extracts of the plant A. mexicana produced a significant activity in cysteamine-induced duodenal ulceration. The aqueous extract at the dose-dependent manner showed the potent activity than methanolic extract. Conclusion: The plant A. mexicana Linn. Increased healing of gastric ulceration and prevented the development of experimentally induced duodenal ulceration in rats.

Evaluation of a new premedication protocol for administration of equine rabies immunoglobulin in patients with hypersensitivity.

OBJECTIVES: The present study was undertaken to standardize skin testing and to develop a safe and effective premedication protocol for administration of ERIG in those with skin test positivity/hypersensitivity. METHODS: A method of grading of skin testing was developed using injection histamine as a positive control. This was evaluated by using it on 517 subjects who had severe (WHO category III) exposure to rabies. A premedication protocol consisting of injections pheniramine, ranitidine, hydrocortisone and adrenaline was evaluated by using it on fifty one subjects who were skin test positive/hypersensitive to ERIG. RESULTS: The premedication protocol was safe and effective as all the S1 subjects could be administered the full dose of ERIG despite being skin test positive/hypersensitive to ERIG. Besides the premedication drugs/protocol did not affect the immune response to vaccine and ERIG therapy.

Antioxidant activity of hydroalcoholic leaf extract of ocimum sanctum in animal models of peptic ulcer.

In the present study, a hydroalcoholic extract of ocimum sanctum leaves has been investigated for its antioxidant activity in animal models of peptic ulcer with the aim of exploring a possible correlation between its antioxidant and antiulcer activities. Gastric ulcers were produced in rats by ethanol treatment and pyloric ligation whereas duodenal ulcers were produced in guinea pigs by histamine treatment. The animals were divided into six groups of six animals each in all these three models of peptic ulcer. Group I served as diseased control in which distilled water (10 ml/kg) orally was administered as placebo. Group II, III and IV received the test drug (ocimum sanctum leaf extract) in doses of 50 mg/kg, 100 mg/kg and 200 mg/ kg respectively orally once daily for 7 days. Group V was administered ranitidine (10 mg/kg orally) once daily for 7 days and served as standard for comparison. Group VI consisted of healthy control for baseline malondialdehyde (MDA) and superoxide dismutase (SOD) levels. The antioxidant activity was by evaluated estimating plasma MDA in ethanol treated rats and histamine treated guinea pigs and estimating SOD in pyloric ligated rats and histamine treated guinea pigs. In ethanol treated rats, ocimum sanctum leaf extract (100 mg/kg & 200 mg/kg) significantly decreased the levels of MDA to 2.45 +/- 0.29 nmole/ml and 2.40 +/- 0.14 nmole/ml respectively in comparison to 4.87 +/- 0.06 in the diseased control. Similarly, in the histamine treated guinea pig group, the same doses of the extract significantly lowered the levels of MDA to 2.45 +/- 0.12 nmole/ml and 2.37 +/- 0.16 nmole/ml respectively when compared to 4.66 +/- 0.11 in the diseased control. The extract (100 mg/kg & 200 mg/ kg) also increased the levels of SOD in pyloric ligated rats to 1.78 +/- 0.12 U/ml and 1.89 +/- 0.08 U/ml respectively when compared to 1.29 +/- 0.06 U/ml in the diseased control. In the histamine treated guinea pig group also, the same doses of the extract produced a rise in the SOD levels to 2.10 +/- 0.11 U/ml and 2.20 +/- 0.14 U/ml respectively when compared to 1.32 +/- 0.07 in the diseased control. Since lowered levels of MDA and increased levels of SOD signify antioxidant activity, the antiulcer activity of ocimum sanctum might be due to this mechanism.

A Randomized, Prospective, Comparative, Multicenter Study of Rabeprazole and Ranitidine in the Treatment of Reflux Esophagitis / 대한소화기학회지

BACKGROUND/AIMS: This study was done to evaluate the efficacy of rabeprazole (proton-pump-inhibitor) and ranitidine (H2-receptor antagonist) in the symptom relief and treatment of erosive esophagitis diagnosed by endoscopy. METHODS: A total of 110 patients with typical gastroesophageal reflux disease (GERD) symptoms were enrolled in this multicenter study. They were randomized into rabeprazole group (53 patients) and ranitidine group (57 patients) respectively. The patients in rabeprazole group were given 10 mg of rabeprazole and ranitidine group received 300 mg of ranitidine before breakfast and dinner for 8 weeks. After the end of treatment, we evaluated the endoscopic healing rate of reflux esophagitis and symptomatic improvement. RESULTS: After 8 weeks of treatment, rabeprazole group showed significantly higher complete endoscopic cure rate than ranitidine group (86.8% [46/53] vs. 57.9% [33/57], p=0.001) and higher symptomatic improvement of heartburn (91.2% [31/34] vs. 76.2% [32/42], p=0.085), especially in the first 7 days (76.7% vs. 45.3%, p=0.008). Also, rabeprazole group showed significantly higher improvement of regurgitation symptom than ranitidine group (100% [35/35] vs. 83% [39/47], p=0.009). Both group showed no differences in the improvement of chest pain and globus sensation. All the adverse events (rabeprazole group 4 events vs. ranitidine group 3 events) were mild and there was no abnormality in laboratory test. CONCLUSIONS: In patients with GERD, rabeprazole 10 mg b.i.d. is superior to ranitidine 300 mg b.i.d. in healing of reflux esophagitis and resolving typical GERD symptoms. Rabeprazole is an effective and well-tolerated drug for GERD treatment.

A Randomized, Comparative Study of Rabeprazole vs. Ranitidine Maintenance Therapies for Reflux Esophagitis: Multicenter Study / 대한소화기학회지

BACKGROUND/AIMS: Reflux esophagitis is a recurring condition for which many patients require maintenance therapy. This comparative, randomized multicenter study was designed to evaluate the effect of long-term maintenance treatment comparing proton pump inhibitor, rabeprazole and H2 receptor antagonist, ranitidine. METHODS: Eighty four patients with healed reflux esophagitis confirmed by endoscopy were randomly allocated to receive maintenance treatment with either rabeprazole 10 mg once daily or ranitidine 300 mg once daily for 32 weeks. Patients were seen every 8 weeks or at symptomatic relapse. RESULTS: Of 84 initially treated patients, 73 entered the maintenance study. The percentage of asymptomatic patients after 90-day and 210-day treatment were 97% and 81.5%, for rabeprazole and 74.3% and 62.3%, for ranitidine, respectively. After 32 weeks, the relapse rates of esophagitis were 21.3% in the rabeprazole group and 62.9% in the ranitidine group (RR: 0.405, 95% CI: 0.215-0.766). CONCLUSIONS: Maintenance treatment with rabeprazole (10 mg once daily) is superior to ranitidine (300 mg once daily) in keeping the patients with reflux esophagitis in remission over a 32 week period.

Childhood Helicobacter pylori infection, clinical presentations, endoscopic, histologic features and results of treatment.

OBJECTIVE: To study childhood Helicobacter pylori infection concerning the clinical presentations, endoscopic, histologic features and results of treatment. MATERIAL AND METHOD: A retrospective study conducted at the Gastroenterology and Nutrition Unit, Queen Sirikit National Institute of Child Health (QSNICH) was done from January 1993 to December 2002. All patients presented with recurrent abdominal pain, upper GI bleeding (non-variceal bleeding) chronic vomiting and dyspeptic symptoms who underwent upper GI endoscopy were included in this study. Positive urease test verified by biopsied specimens from the gastric antrum and body and/or finding the organisms from the specimens were the criteria for diagnosis of H. pylori infection. Clinical presentations, endoscopic, histologic features and results of treatment in H. pylori infected cases were described. RESULT: A total of 144 patients who underwent upper GI endoscopy were included in the study. 22 out of 144 cases proved to be infected by H. pylori. Ages ranged from 2.6 to 14 years (mean age 9 years). The male/female ratio was 1:1.2. Vomiting and epigastric pain were the leading symptoms. Endoscopic findings were divided into inflammation in the stomach 12 cases, both stomach and duodenum 6 cases and duodenal ulcer 4 cases. Nodular hyperplasia of gastric antrum was found in 8 out of 22 cases. Histologic evidence of chronic gastritis was present in 12 cases, chronic gastroduodenitis 6 cases and chronic duodenitis in duodenal ulcer cases. Treatment regimen consisted of one H2 blocker (ranitidine) initially which was changed to omeprazole in 2001 combined with 2 antibiotics (amoxycillin and metronidazole) for 14 days. CONCLUSION: This study group represented middle and low income groups from around Bangkok and many parts of Thailand. The prevalence of H. pylori infection in the present study was 15.3 per cent which reflects that H. pylori infection is a common health problem in Thailand. However, because this was only a descriptive study, the authors cannot specify the association between symptoms, endoscopic findings, histologic features and disease.

Stress ulcer prophylaxis in patients on ventilator.

The objective of the study was to assess the efficacy of the H2-receptor antagonists and sucralfate for the prophylaxis of stress ulcer in patients on a ventilator in an intensive care unit in the general intensive care unit of our institute. A randomized, clinical controlled trial was conducted. Fifty-two critically ill patients, who required mechanical ventilation for more than 24 hours, were randomly divided into 3 groups. Group I received ranitidine 50 mg (intravenous) 8 hourly, group II received tablet sucralfate 1 g 8 hourly through a Ryle's tube, whereas group III was not given any drug. The incidence of upper gastrointestinal bleed, change in gastric pH and growth of gram-negative organisms in the gastric juice and bronchoalveolar lavage (BAL) culture were noted and analysed. The treatment groups were similar with respect to the baseline characteristics. The incidence of upper gastrointestinal bleeding was similar in the ranitidine (12.5%) and sucralfate groups (14.35%) but was high in the control group (57.14%). The mean gastric pH was significantly low in the control group (mean pH 2.07) compared to the ranitidine (mean pH 5.25) and sucralfate groups(mean pH 3.54)(p < 0.05). The incidence of positive culture for gram-negative organisms was significantly high in the ranitidine group (75%) in comparison with the sucralfate group (33.33%) (p < 0.002). However, the incidence of positive growth in the BAL culture was similar in all three groups. We conclude that both ranitidine and sucralfate are equally effective in decreasing the incidence of upper gastrointestinal haemorrhage and other stress- related lesions. Though ranitidine was more effective in increasing the gastric pH, the incidence of gastric colonization was higher in the ranitidine group compared to the sucralfate group.

Impact of ranitidine on prognosis after simple closure of perforated duodenal ulcer.

AIM: This randomized controlled study was carried out to evaluate the role of H2 receptor antagonists after simple closure of perforated duodenal ulcer. METHODS: A total of 192 patients who underwent simple closure for perforated duodenal ulcer were divided into two groups (A: study group and B: control group). Group A patients were treated with H2 receptor antagonists, while the patients in group B received placebo. Only 174 patients were available for endoscopic follow up. RESULTS: At the end of 24 weeks, only 6 patients out of 90 (6.6%) in group A as compared to 18 patients out of 84 (21.4%) in group B had persistent symptoms of ulcer disease as well as endoscopically proven ulcer (p < 0.05). CONCLUSIONS: The results indicate that H2 receptor antagonists have a definite role and endoscopic follow up is mandatory to define those cases who actually need definitive surgery.

Avaliaçäo da eficácia da ranitidina na esofagite da refluxo em crianças e adolescentes / Evaluation of efficacy of ranitidine in reflux esophagitis in children and adolescents

Foi realizado ensaio terapêutico aberto, não controlado, prospectivo e consecutivo em 49 crianças e adolescentes de 1 a 1 m 17 a 3m (mediana= 7 a 8m) de ambos os sexos com esofagite de refluxo. Administrou-se ranitidina (4mg/kg) em 2 doses durante 8 semanas, associada à terapia postural e dietética. Após o diagnostico endoscópico de esofagite, os pacientes foram avaliados clinicamente antes e durante o tratamento: após 8, 15, 30 e 60 dias. Endoscopia de controle foi realizada após 60 dias. Do total de 49 pacientes, 40 completaram o estudo. A eficácia foi avaliada através da evolução clinica e dos achados endoscópicos. Helicobacter pylori foi detectado em 40 por cento dos pacientes. Houve regressão total ou parcial dos sintomas em 96 por cento dos pacientes e melhora ou cura endoscópica em 81,5 por cento; porém levando-se em consideração o grau de esofagite, o tratamento foi eficaz em 86 por cento da esofagite grau I comparados a 43 por cento da esofagite grau II. Na esofagite grau II, recomendamos a ranitidina por período de tempo mais prolongado (12 semanas). O controle endoscópico deve ser sempre realizado na esofagite grau II e III, uma vez que a remissão dos sintomas não corresponde a cura endoscópica. Do total de 38 pacientes, 50 por cento foram considerados curados, 45 por cento melhorados e 5 por cneto inalterados. Considerando que a esofagite grau I predomina na criança, a ranitidina pode ser utilizada na grande maioria dos pacientes pediátricos com esofagite de refluxo.

Seasonal behaviour of healed duodenal ulcer.

Incidence of peptic ulcer is more in people living at higher altitude and similarly relapse of healed duodenal ulcer is more in winter season. Seasonal behaviour of healed duodenal ulcer with or without maintenance therapy with H2 blockers was studied among subjects residing around Shimla (approximate altitude 7000 feet above mean sea level). Sixty-four subjects of endoscopically healed duodenal ulcer were alternatively advised placebo (32 subjects) and ranitidine 150 mg (32 subjects) at bed time as maintenance therapy for period of one year. Subjects were reviewed endoscopically and evaluated for H pylori by rapid urease test, every months or earlier if symptomatic. Relapse rate was analysed among 60 subjects at the end of one year. Cumulative relapse rate was found 60% in ranitidine group and 100% in placebo group. In ranitidine group percentage of relapse to number of endoscopic examinations was 21.4% throughout the year, but in placebo group during winter and spring season relapse was 87.5% of endoscopic examination whereas 57.2% during summer and fall season. Incidence of duodenal ulcer relapse without maintenance therapy was more in winter and spring season (October to March) as compared to summer and fall (April to September), whereas intermittent seasonal treatment is efficacious in prevention of duodenal ulcer relapse and also improves cost benefit ratio of ulcer treatment.

Natural history of severe duodenal ulcer disease.

BACKGROUND: A subset of patients with chronic duodenal ulcer has severe ulcer diathesis in the form of frequent relapses and complications like perforation and hemorrhage. We observed the effect of drug treatment on the natural history of this subset. METHODS: Of 526 patients diagnosed to have chronic duodenal ulcer by endoscopy, 23 patients with severe diathesis were available for long follow-up (mean period 36 months). Each patient was assessed clinically and endoscopically every 2 months for at least 12 months and then every 3 months or when symptomatic. Helicobacter pylori status was assessed during endoscopy. The effect of antisecretory drugs and anti-H. pylori therapy on natural history was determined. RESULTS: Thirteen of 23 patients (56%) had refractory ulcers; six responded to double dose of H2-receptor antagonists (H2RA) for 8 weeks and six to omeprazole 40 mg daily for 4-8 weeks. Of 20 patients (87%) who were H. pylori-positive, 15 completed triple-drug therapy; of these, 10 patients eradicated H. pylori. These 10 patients were followed up for 24 months; there were no ulcer relapses within the first 12 months but 8 of them relapsed between 12 and 24 months (total number of relapses 8). Reinfection with H. pylori occurred in 3 patients. In the other 10 patients who remained H. pylori-positive, there were 19 episodes of ulcer relapse in 7 patients over 24 months, in spite of maintenance therapy with H2RA (p < 0.05). CONCLUSIONS: Refractoriness in patients with severe ulcer disease is usually episodic and amenable to larger doses of omeprazole or H2RA. Anti-H. pylori therapy improves the natural history but its effect in preventing ulcer relapse is short lasting (less than 12 months). Recurrence of infection is a problem in our population.

A randomized clinical trial comparing the efficacy of ranitidine and famotidine on intragastric acidity in critically ill pediatric patients.

We examined the efficacy of intravenous ranitidine and famotidine on raising intragastric pH in each of 10 critically ill pediatric patients. The severity of illness was assessed by using the modified zinner index score. The study had 3 phases and each phase took 24 hours. Intragastric pH was measured by continuous pH monitoring digitrapper for 72 hours. In phase 1 and 3, the patients did not receive any H2 blockers. In phase 2, they were randomized to receive intravenous ranitidine or famotidine. The majority of cases had intragastric pH < 4 in day 1 (base line). Ranitidine and famotidine increased total time of intragastric pH > or = 4 from the base line during day 2, 38.2 +/- 16.9 per cent and 60.3 +/- 24.8 per cent respectively (P0.004), but there was no statistical difference between the 2 medications in both Zinner index score 1 and score greater than 1 group (P 0.08, 0.45). Three cases in the famotidine group had successful prophylaxis with total time pH > or = 4 more than 80 per cent. Famotidine appeared to have a trend toward increasing intragastric pH in critically ill pediatric patients.